Identification of hypothalamic arcuate nucleus-specific enhancer region of Kiss1 gene in mice

Teppei Goto, Junko Tomikawa, Kana Ikegami, Shiori Minabe, Hitomi Abe, Tatsuya Fukanuma, Takuya Imamura, Kenji Takase, Makoto Sanbo, Koichi Tomita, Masumi Hirabayashi, Kei Ichiro Maeda, Hiroko Tsukamura, Yoshihisa Uenoyama

研究成果: ジャーナルへの寄稿記事

8 引用 (Scopus)

抄録

Pulsatile secretion of GnRH plays a pivotal role in follicular development via stimulating tonic gonadotropin secretion in mammals. Kisspeptin neurons, located in the arcuate nucleus (ARC), are considered to be an intrinsic source of the GnRH pulse generator. The present study aimed to determine ARC-specific enhancer(s) of the Kiss1 gene by an in vivo reporter assay. Three green fluorescent protein (GFP) reporter constructs (long, medium length, and short) were generated by insertion of GFP cDNA at the Kiss1 locus. Transgenic female mice bearing the long and mediumlength constructs showed apparent GFP signals in kisspeptin-immunoreactive cells in both the ARC and anteroventral periventricular nucleus, in which another population of kisspeptin neurons are located. On the other hand, transgenic mice bearing 5′-truncated short construct showed few GFP signals in the ARC kisspeptin-immunoreactive cells, whereas they showed colocalization of GFPand kisspeptin-immunoreactivities in the anteroventral periventricular nucleus. In addition, chromatin immunoprecipitation and chromosome conformation capture assays revealed recruitment of unoccupied estrogen receptor-α in the 5′-upstream region and intricate chromatin loop formation between the 5′-upstream and promoter regions of Kiss1 locus in the ARC. Taken together, the present results indicate that 5′-upstream region of Kiss1 locus plays a critical role in Kiss1 gene expression in an ARC-specific manner and that the recruitment of estrogen receptor-α and formation of a chromatin loop between the Kiss1 promoter and the 5′ enhancer region may be required for the induction of ARC-specific Kiss1 gene expression. These results suggest that the 5′-upstream region of Kiss1 locus functions as an enhancer for ARC Kiss1 gene expression in mice.

元の言語英語
ページ(範囲)121-129
ページ数9
ジャーナルMolecular Endocrinology
29
発行部数1
DOI
出版物ステータス出版済み - 1 1 2015

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Arcuate Nucleus of Hypothalamus
Kisspeptins
Green Fluorescent Proteins
Genes
Anterior Hypothalamus
Gene Expression
Gonadotropin-Releasing Hormone
Estrogen Receptors
Transgenic Mice
Chromatin
Neurons
Chromatin Immunoprecipitation
Gonadotropins
Genetic Promoter Regions
Mammals
Complementary DNA
Chromosomes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Endocrinology

これを引用

Goto, T., Tomikawa, J., Ikegami, K., Minabe, S., Abe, H., Fukanuma, T., ... Uenoyama, Y. (2015). Identification of hypothalamic arcuate nucleus-specific enhancer region of Kiss1 gene in mice. Molecular Endocrinology, 29(1), 121-129. https://doi.org/10.1210/me.2014-1289

Identification of hypothalamic arcuate nucleus-specific enhancer region of Kiss1 gene in mice. / Goto, Teppei; Tomikawa, Junko; Ikegami, Kana; Minabe, Shiori; Abe, Hitomi; Fukanuma, Tatsuya; Imamura, Takuya; Takase, Kenji; Sanbo, Makoto; Tomita, Koichi; Hirabayashi, Masumi; Maeda, Kei Ichiro; Tsukamura, Hiroko; Uenoyama, Yoshihisa.

:: Molecular Endocrinology, 巻 29, 番号 1, 01.01.2015, p. 121-129.

研究成果: ジャーナルへの寄稿記事

Goto, T, Tomikawa, J, Ikegami, K, Minabe, S, Abe, H, Fukanuma, T, Imamura, T, Takase, K, Sanbo, M, Tomita, K, Hirabayashi, M, Maeda, KI, Tsukamura, H & Uenoyama, Y 2015, 'Identification of hypothalamic arcuate nucleus-specific enhancer region of Kiss1 gene in mice', Molecular Endocrinology, 巻. 29, 番号 1, pp. 121-129. https://doi.org/10.1210/me.2014-1289
Goto, Teppei ; Tomikawa, Junko ; Ikegami, Kana ; Minabe, Shiori ; Abe, Hitomi ; Fukanuma, Tatsuya ; Imamura, Takuya ; Takase, Kenji ; Sanbo, Makoto ; Tomita, Koichi ; Hirabayashi, Masumi ; Maeda, Kei Ichiro ; Tsukamura, Hiroko ; Uenoyama, Yoshihisa. / Identification of hypothalamic arcuate nucleus-specific enhancer region of Kiss1 gene in mice. :: Molecular Endocrinology. 2015 ; 巻 29, 番号 1. pp. 121-129.
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abstract = "Pulsatile secretion of GnRH plays a pivotal role in follicular development via stimulating tonic gonadotropin secretion in mammals. Kisspeptin neurons, located in the arcuate nucleus (ARC), are considered to be an intrinsic source of the GnRH pulse generator. The present study aimed to determine ARC-specific enhancer(s) of the Kiss1 gene by an in vivo reporter assay. Three green fluorescent protein (GFP) reporter constructs (long, medium length, and short) were generated by insertion of GFP cDNA at the Kiss1 locus. Transgenic female mice bearing the long and mediumlength constructs showed apparent GFP signals in kisspeptin-immunoreactive cells in both the ARC and anteroventral periventricular nucleus, in which another population of kisspeptin neurons are located. On the other hand, transgenic mice bearing 5′-truncated short construct showed few GFP signals in the ARC kisspeptin-immunoreactive cells, whereas they showed colocalization of GFPand kisspeptin-immunoreactivities in the anteroventral periventricular nucleus. In addition, chromatin immunoprecipitation and chromosome conformation capture assays revealed recruitment of unoccupied estrogen receptor-α in the 5′-upstream region and intricate chromatin loop formation between the 5′-upstream and promoter regions of Kiss1 locus in the ARC. Taken together, the present results indicate that 5′-upstream region of Kiss1 locus plays a critical role in Kiss1 gene expression in an ARC-specific manner and that the recruitment of estrogen receptor-α and formation of a chromatin loop between the Kiss1 promoter and the 5′ enhancer region may be required for the induction of ARC-specific Kiss1 gene expression. These results suggest that the 5′-upstream region of Kiss1 locus functions as an enhancer for ARC Kiss1 gene expression in mice.",
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AU - Goto, Teppei

AU - Tomikawa, Junko

AU - Ikegami, Kana

AU - Minabe, Shiori

AU - Abe, Hitomi

AU - Fukanuma, Tatsuya

AU - Imamura, Takuya

AU - Takase, Kenji

AU - Sanbo, Makoto

AU - Tomita, Koichi

AU - Hirabayashi, Masumi

AU - Maeda, Kei Ichiro

AU - Tsukamura, Hiroko

AU - Uenoyama, Yoshihisa

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